公开(公告)号：KR100930586B1

公开(公告)日：2009-12-09

申请号：KR1020070120038

申请日：2007-11-23

Applicant: 한국화학연구원 ,  국제약품 주식회사

Inventor： 김봉진 ,  송복주 ,  권지웅 ,  공재양 ,  조희영 ,  최영로 ,  이동우

IPC: C07D477/20

CPC classification number: Y02A50/473

Abstract: 본 발명은 2-아릴메틸아제티딘-카바페넴-3-카복실산의 3번 위치에 특정 구조에 화합물을 에스테르 결합으로 도입한 2-아릴메틸아제티딘-카바페넴-3-카복실산 유도체, 이의 제조방법 및 이를 포함하는 약학 조성물을 제공한다. 상기 2-아릴메틸아제티딘-카바페넴-3-카복실산 유도체는 높은 경구흡수율을 나타냄으로써 경구투여가 가능하며, 그의 활성 대사체는 그람 양성균 및 그람 음성균에 대하여 광범위한 항균 활성을 나타내며, MRSA (메티실린 내성균주) 및 QRS (퀴놀론 내성균주)에 대한 우수한 항균 활성을 나타낸다.
카바페넴

Abstract translation: 本发明是为了介绍在以下羧酸的3位上的特定结构的酯键的2-芳基甲基 - 氮杂环丁烷咔唑青霉烯-3-羧酸衍生物，方法它们的制备2-芳基甲基 - 氮杂环丁烷咔唑青霉烯-3-酮化合物和 和包含其的药物组合物。 通过表达高的口服吸收的2-芳基甲基 - 氮杂环丁烷咔唑青霉烯-3-羧酸衍生物，以及可以口服给药，其活性代谢物显示了针对革兰氏阳性和革兰氏阴性细菌具有广泛的抗菌活性，MRSA（耐甲氧西林 耐药菌株）和QRS（喹诺酮耐药菌株）。

公开(公告)号：KR1020080094475A

公开(公告)日：2008-10-23

申请号：KR1020070038962

申请日：2007-04-20

Applicant: 한국화학연구원

Inventor： 공재양 ,  박우규 ,  조희영 ,  정대영 ,  최길돈 ,  배애님

IPC: A61K31/551 ,  A61K31/435 ,  A61K31/40 ,  A61P25/18

CPC classification number: A61K31/4468 ,  A61K9/0095 ,  A61K9/08 ,  A61K9/10 ,  A61K9/20 ,  A61K9/48 ,  A61K31/40 ,  A61K31/495 ,  A61K31/496 ,  A61K31/551

Abstract: 12 compounds are provided to show excellent binding affinity to serotonin 5-HT2A receptor, thereby being usefully used as a prophylactic or a therapeutic agent of central nervous system diseases such as anxiety, hypochondria, stroke, neurosis, psychosis, schizophrenia, suicidal tendency, Alzheimer's disease, Parkinson's disease, Huntington's chorea, sleep disorders, appetite disorders, cocaine, withdrawal symptoms caused by drug abuse, and migraine. A pharmaceutical composition for preventing and treating central nervous system diseases related to serotonin 5-HT2A receptor comprises a compound selected from the group consisting of naphthalene-2-sulfonic acid methyl-(1-methyl-piperidin-4-yl)-amide, 1-(5-bromo-2-methoxy-benzenesulfonyl)-4-(2-thiopen-2-yl-ethyl)-piperazine, 1-(1-benzyl-piperidin-4-yl)-3-(4-trifluoromethylsulfanyl-phenyl)-urea, 8-[4-(3-phenyl-aryl)-piperazin-1-sulfonyl]-quinoline, 1-(1-benzyl-pyrrolidin-3-yl)-3-(4-trifluoromethylsulfanyl-phenyl)-urea, 1-(4-butoxy-benzenesulfonyl)-4-methyl-[1,4]diazepane, 1-[4-(3,4-dimethyl-phenyl)-piperazin-1-yl]-3-phenoxy]-propan-2-one, biphenyl-4-sulfonic acid [2-(1-methyl-pyrrolidin-2-yl)-ethyl]-amide, 1-(2,5-dichloro-benzenesulfonyl)-4-penethyl-piperazine, 1-penethyl-4-(toluene-4-sulfonyl)-piperazine, 1-(2-fluoro-5-methyl-benzenesulfonyl)-4-penethyl-piperazine, and 1-(4-bromo-benzenesulfonyl)-4-penethyl-piperazine or a pharmaceutically acceptable salt thereof. The composition is formulated into tablet, capsule, solution, syrup, suspension and injection.

Abstract translation: 提供了12种化合物以显示与5-羟色胺5-HT2A受体的极好的结合亲和力，从而有效地用作中枢神经系统疾病如焦虑症，hypochondria，中风，神经症，精神病，精神分裂症，自杀倾向，阿尔茨海默氏症的预防或治疗剂 疾病，帕金森病，亨廷顿舞蹈病，睡眠障碍，食欲障碍，可卡因，药物滥用引起的戒断症状和偏头痛。 用于预防和治疗与5-羟色胺5-HT 2A受体相关的中枢神经系统疾病的药物组合物包括选自萘-2-磺酸甲基 - （1-甲基 - 哌啶-4-基） - 酰胺，1 - （5-溴-2-甲氧基 - 苯磺酰基）-4-（2-噻吩-2-基 - 乙基） - 哌嗪，1-（1-苄基 - 哌啶-4-基）-3-（4-三氟甲硫基 - 苯基） - 脲，8- [4-（3-苯基 - 芳基） - 哌嗪-1-磺酰基] - 喹啉，1-（1-苄基 - 吡咯烷-3-基）-3-（4-三氟甲硫基 - 苯基） - 脲，1-（4-丁氧基苯磺酰基）-4-甲基 - [1,4]二氮杂环庚烷，1- [4-（3,4-二甲基 - 苯基） - 哌嗪-1-基] -3-苯氧基] - 丙-2-酮，联苯-4-磺酸[2-（1-甲基 - 吡咯烷-2-基） - 乙基] - 酰胺，1-（2,5-二氯 - 苯磺酰基）-4-苯乙基 - 哌嗪 ，1-苯乙基-4-（甲苯-4-磺酰基） - 哌嗪，1-（2-氟-5-甲基 - 苯磺酰基）-4-辛基 - 哌嗪和1-（4-溴 - 苯磺酰基）-4- 哌嗪或其药学上可接受的盐。 将组合物配制成片剂，胶囊，溶液，糖浆，悬浮液和注射剂。

公开(公告)号：KR100808685B1

公开(公告)日：2008-02-29

申请号：KR1020060101544

申请日：2006-10-18

Applicant: 한국화학연구원

Inventor： 공재양 ,  최일영 ,  임희종 ,  명도 ,  정명희 ,  박우규

IPC: C07D401/08 ,  C07D417/08 ,  C07D413/08

Abstract: A novel piperazine derivative is provided to show excellent antagonism against a dopamine receptor D4, thereby being effective as a therapeutic agent for schizophrenia. A piperazine derivative having a cycloalkyl bicyclic heterocycle group is represented by a formula(1), where R1 is a group represented by the structural formula(1) or (2); X is H, halogen, nitro, cyano, C1-6 alkyl, or C1-6 alkoxy; Y is NH, S or O; R2 is phenyl or pyridine, which may be substituted or unsubstituted by a substituent selected from the group consisting of halogen, C1-6 alkyl, C1-6 alkoxy, and cyano; n is an integer from 1 to 3. A method for preparing a piperazine compound represented by the formula(1b) comprises the steps of: (a) subjecting cyclopentanone carboxylic acid coupled to a Wang resin and represented by the formula(3) with a piperazine to a reducing amination to obtain a compound represented by the formula(3a); and (b) applying microwave to the compound of the formula(3a) with an amine compound represented by the formula(3b) to synthesize the compound of the formula(1b), where R2, X, Y, and n are the same as defined above, and A is Wang resin. A therapeutic agent for schizophrenia comprises the compound of the formula(1) or a pharmaceutically acceptable salt thereof.

Abstract translation: 提供了一种新的哌嗪衍生物，以显示对多巴胺受体D4的极好的拮抗作用，从而作为精神分裂症的治疗剂是有效的。 具有环烷基双环杂环基的哌嗪衍生物由式（1）表示，其中R 1是由结构式（1）或（2）表示的基团。 X是H，卤素，硝基，氰基，C 1-6烷基或C 1-6烷氧基; Y是NH，S或O; R2是苯基或吡啶，其可以被选自卤素，C 1-6烷基，C 1-6烷氧基和氰基的取代基取代或未取代。 n为1〜3的整数。由式（1b）表示的哌嗪化合物的制备方法包括以下步骤：（a）将与式（3）表示的Wang树脂偶联的环戊酮羧酸与 哌嗪还原胺化得到式（3a）表示的化合物; 和（b）用式（3b）表示的胺化合物向式（3a）化合物施加微波以合成式（1b）化合物，其中R 2，X，Y和n与 A为王树脂。 精神分裂症的治疗剂包括式（1）的化合物或其药学上可接受的盐。

公开(公告)号：KR1020080018029A

公开(公告)日：2008-02-27

申请号：KR1020060080067

申请日：2006-08-23

Applicant: 한국화학연구원

Inventor： 정영식 ,  박노상 ,  박우규 ,  공재양

IPC: A61K31/216 ,  A61P25/08

Abstract: Muscarinic receptor antagonists or agents are provided to struggle with the muscarinic receptor, prevent and treat nervous system diseases such as convulsion, Parkinson's disease and epilepsy, and detoxify the poisoning of nerve agents or organophosphate fertilizer. The muscarinic receptor antagonists or agents contain 2-phenyl-2-carboxylic acid derivatives represented by the formula(1) or pharmaceutically acceptable salts thereof as effective ingredients, wherein X is hydrogen, halogen, amino, nitro, C1-C5 linear or branched chain alkyl or C1-C5 alkoxy and is positioned in an ortho-, metha- or para-site; Y is C1-C7 linear or branched chain alkyl; R1 and R2 are each independently C1-C7 linear or branched chain alkyl and form a ring together; and n is an integer from 1 to 4.

Abstract translation: 提供毒蕈碱受体拮抗剂或药物与毒蕈碱受体作斗争，预防和治疗神经系统疾病如惊厥，帕金森病和癫痫，并解毒神经药物或有机磷酸盐肥料的中毒。 毒蕈碱受体拮抗剂或药剂含有由式（1）表示的2-苯基-2-羧酸衍生物或其药学上可接受的盐作为有效成分，其中X为氢，卤素，氨基，硝基，C 1 -C 5直链或支链 烷基或C 1 -C 5烷氧基并位于邻位，间位或对位; Y是C 1 -C 7直链或支链烷基; R1和R2各自独立地为C1-C7直链或支链烷基并形成环; n为1〜4的整数。

公开(公告)号：KR1020080004304A

公开(公告)日：2008-01-09

申请号：KR1020060063140

申请日：2006-07-05

Applicant: 한국화학연구원

Inventor： 성철민 ,  박노상 ,  최진일 ,  박철민 ,  박우규 ,  공재양

IPC: C07D401/04 ,  C07D403/04 ,  A61P25/00

Abstract: A novel substituted-1H-quinazoline-2,4-dione derivative is provided which shows excellent selectivity to a 5-HT6 receptor compared to other receptors, and inhibits the concentration increase of cAMP caused by 5-HT and apomorphine -induced hyperactivity of a rat, thereby being usefully used for central nervous system diseases related to the 5-HT6 receptor. A method for preparing a substituted-1H-quinazoline-2,4-dione derivative represented by the formula(1) comprises the steps of: (a) reacting anthranilic acid anhydride represented by the formula(2) with an amine compound to prepare an intermediate represented by the formula(I); (b) subjecting the intermediate of the formula(I) to cyclization to obtain an intermediate represented by the formula(II); (c) reacting the intermediate of the formula(II) with a compound represented by the formula(5) to prepare the derivative of the formula(1). In the formulae, each R^1, R^2 and R^3 is independently H, halogen, amino, cycloamino, nitro, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, piperazinyl, or N-methyl piperazinyl; R^4 is H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkoxy, aryloxy, acyl amino, arylsulfonylamino, arylsulfonylureido, alkylcarboxylate, arylcarboxylate, aralkylcarboxylate, alkylureido, or arylureido; R^5 is H, alkyl, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; R^6 is H, alkyl or aryl; X is F, Cl, Br, I or trifluoroacetate; and Y is Cl, Br, I, methane sulfonate, or p-toluenesulfonate. A pharmaceutical composition as an antagonist of 5-HT6 serotonin receptor comprises the compound of the formula(1), a pharmaceutically acceptable salt thereof or a prodrug thereof as an effective ingredient.

Abstract translation: 提供了一种新的取代的1H-喹唑啉-2,4-二酮衍生物，其与其他受体相比显示出对5-HT6受体的优异选择性，并且抑制由5-HT引起的cAMP和阿扑吗啡诱导的多动症的浓度增加 大鼠，因此有用地用于与5-HT6受体相关的中枢神经系统疾病。 由式（1）表示的取代的1H-喹唑啉-2,4-二酮衍生物的制备方法包括以下步骤：（a）使式（2）所示的邻氨基苯甲酸酐与胺化合物反应，制备 由式（I）表示的中间体; （b）使式（I）的中间体环化以获得由式（II）表示的中间体; （c）使式（II）的中间体与由式（5）表示的化合物反应以制备式（1）的衍生物。 式中，R 1，R 2和R 3各自独立地为H，卤素，氨基，环氨基，硝基，氰基，烷基，卤代烷基，烷氧基，卤代烷氧基，哌嗪基或N-甲基哌嗪基; 酰基氨基，芳基磺酰基氨基，芳基磺酰基脲基，烷基羧酸酯，芳基羧酸酯，芳烷基羧酸酯，烷基脲基或芳基脲基; R 4是H，烷基，环烷基，卤代烷基，芳基，杂芳基，芳烷基，杂芳基烷基，烷氧基， R 5是H，烷基，环烷基，卤代烷基，芳基，芳基烷基，杂芳基或杂芳基烷基; R 6是H，烷基或芳基; X是F，Cl，Br，I或三氟乙酸盐; Y是Cl，Br，I，甲磺酸盐或对甲苯磺酸盐。 作为5-HT 6 5-羟色胺受体的拮抗剂的药物组合物包含式（1）的化合物，其药学上可接受的盐或其前药作为有效成分。

公开(公告)号：KR100753907B1

公开(公告)日：2007-08-31

申请号：KR1020060037547

申请日：2006-04-26

Applicant: 한국화학연구원

Inventor： 정영식 ,  성철민 ,  박노상 ,  최진일 ,  공재양 ,  박우규

IPC: C07C219/12 ,  C07D211/40 ,  C07D451/04

Abstract: Provided are a novel 2-phenylindane-2-carboxylic acid ester derivative and its pharmaceutically acceptable salt, a method for preparing the derivative, and an agent for treating or preventing convulsions, Parkinson's disease or epilepsy containing the derivative. A 2-phenylindane-2-carboxylic acid ester derivative is represented by a formula 1, wherein X is H, a halogen atom, an amino group, a nitro group, a substituted or unsubstituted C1-C5 linear or branched alkyl group, or a substituted or unsubstituted C1-C5 alkoxy group; Y is a substituted or unsubstituted C1-C7 linear or branched alkyl group, or a substituted or unsubstituted C3-C7 cycloalkyl group; Z is H, a halogen atom, a substituted or unsubstituted C1-C5 alkyl group, a substituted or unsubstituted C1-C5 alkoxy group, or a substituted or unsubstituted C5-C7 cycloalkyl or aryl group fused with the two carbon atoms adjacent to the benzene ring of the indane ring; and R1 and R2 are independently a substituted or unsubstituted C1-C7 alkyl group, can form a ring together, or can independently form a ring together with Y.

Abstract translation: 本发明提供一种新的2-苯基茚满-2-羧酸酯衍生物及其药学上可接受的盐，该衍生物的制备方法，以及含有该衍生物的惊厥，帕金森氏病或癫痫的治疗或预防剂。 2-苯基茚满-2-羧酸酯衍生物由式1表示，其中X为H，卤素原子，氨基，硝基，取代或未取代的C1-C5直链或支链烷基或 取代或未取代的C 1 -C 5烷氧基; Y是取代或未取代的C 1 -C 7直链或支链烷基，或取代或未取代的C 3 -C 7环烷基; Z是H，卤素原子，取代或未取代的C1-C5烷基，取代或未取代的C1-C5烷氧基，或取代或未取代的C5-C7环烷基或芳基，其与苯相邻的两个碳原子 茚满环的环; 并且R 1和R 2独立地为取代或未取代的C 1 -C 7烷基，可以一起形成环，或者可以与Y一起独立地形成环。

公开(公告)号：KR1020070045063A

公开(公告)日：2007-05-02

申请号：KR1020050101516

申请日：2005-10-26

Applicant: 한국화학연구원

Inventor： 하재두 ,  조성윤 ,  조희영 ,  공재양 ,  최중권

IPC: C07D487/04

Abstract: 본 발명은 항종양 활성을 갖는 [1,2,4]-트리아졸로[4,3-c]퀴나졸린 유도체에 관한 것으로, 더욱 상세하게는 티로신 키나제에 대한 억제활성이 우수하여 비정상적인 키나제의 활성으로 야기되는 질환 예를 들면 암, 특히 결장직장암, 유방암, 폐암, 전립선암, 췌장암, 방광암, 신장암, 백혈병, 림프종과 같은 고증식성 질환 치료에 유효한 신규 구조의 [1,2,4]-트리아졸로[4,3-c]퀴나졸린 유도체 및 이의 약학적으로 허용 가능한 염과, 이 화합물의 의약적 용도에 관한 것이다.

公开(公告)号：KR1020050108567A

公开(公告)日：2005-11-17

申请号：KR1020040033474

申请日：2004-05-12

Applicant: 한국화학연구원

Inventor： 김봉진 ,  김재학 ,  김광호 ,  정희정 ,  전미애 ,  공재양 ,  조희영

IPC: C07D477/20

CPC classification number: Y02P20/55 ,  C07D477/18 ,  C07D477/20

Abstract: 본 발명은 그람양성균 및 그람음성균에 대해 광범위하게 항균효과를 나타내며, 메티실린 내성 스타필로코쿠스 아우레우스(methicillin resistant staphylococcus aureus, MRSA)를 비롯한 내성균에도 우수한 항균효과를 갖는 하기 화학식 1의 카바페넴 유도체, 이의 제조 방법 및 이를 함유하는 항생제 조성물에 관한 것이다.

상기 식에서, R
1 , R
2 및 R
3 는 각각 독립적으로, 수소, 탄소수 1-3개의 알킬기를 의미하며, M은 수소 또는 약리학적으로 허용가능한 염을 형성하는 짝이온을 나타낸다.

公开(公告)号：KR100524701B1

公开(公告)日：2005-10-31

申请号：KR1020030057713

申请日：2003-08-20

Applicant: 한국화학연구원

Inventor： 공영대 ,  이일영 ,  김상요 ,  이진영 ,  김군도 ,  공재양

IPC: C07D239/54 ,  A61K31/505

Abstract: 본 발명은 5-이미노메틸기가 치환된 2,4-피리미딘다이온 유도체에 관한 것으로서, 더욱 상세하게는 2,4-피리미딘다이온 모핵의 C-5 위치에 다양한 이미노메틸기가 치환되어 있는 신규 화합물로서 수용체 티로신 키나제(RTK)로서의 상피세포 성장인자 수용체(EGFR)에 대한 우수한 억제활성을 나타내는 5-이미노메틸기가 치환된 2,4-피리미딘다이온 유도체에 관한 것이다.

상기 화학식 1에서, R
1 , R
2 , R
3 , R
4 및 R
5 는 각각 발명의 상세한 설명에서 정의한 바와 같다.

公开(公告)号：KR1020050020066A

公开(公告)日：2005-03-04

申请号：KR1020030057713

申请日：2003-08-20

Applicant: 한국화학연구원

Inventor： 공영대 ,  이일영 ,  김상요 ,  이진영 ,  김군도 ,  공재양

IPC: C07D239/54 ,  A61K31/505

Abstract: PURPOSE: Derivatives of 5-(iminomethyl)-2,4-pyrimidinedione are provided, which derivatives have activity inhibiting EGFR(epidermal growth factor receptor), so that they can be useful for treatment of cancer. CONSTITUTION: The derivatives of 5-(iminomethyl)-2,4-pyrimidinedione represented by formula (1) are provided, wherein R1 and R2 are independently hydrogen, optionally substituted C1-C10 alkyl or C3-C6 cycloalkyl, or optionally substituted C7-C15 benzyl; R3 and R4 are independently hydrogen, allyl, optionally substituted C1-C10 alkyl or C3-C6 cycloalkyl, optionally substituted C7-C15 benzyl, optionally substituted C6-C15 aryl, optionally substituted C6-C15 hetero atom containing ring, optionally substituted C3-C20 acyl, optionally substituted C3-C20 amide, or optionally substituted C3-C20 thioamide; and R5 is optionally substituted C1-C20 alkyl or C3-C6 cycloalkyl, optionally substituted C7-C15 benzyl, optionally substituted C6-C15 aryl, optionally substituted C6-C15 hetero atom containing ring, optionally substituted C1-C10 alkoxy, optionally substituted C7-C15 benzyloxy, optionally substituted C1-C10 amine, or cyano, provided that the substituent of R1, R2, R3, R4 and R5 is selected from halogen atom, cyano, amide, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, alkylsulfone and arylsulfone, and a case that R3 and R4 are hydrogen simultaneously, and R5 is methyl, hydroxy, phenyl or phenylamine is excluded.

Abstract translation: 目的：提供5-（亚氨基甲基）-2,4-嘧啶二酮的衍生物，该衍生物具有抑制EGFR（表皮生长因子受体）的活性，因此可用于治疗癌症。 构成：提供由式（1）表示的5-（亚氨基甲基）-2,4-嘧啶二酮的衍生物，其中R1和R2独立地为氢，任选取代的C 1 -C 10烷基或C 3 -C 6环烷基，或任选取代的C7- C15苄基; R 3和R 4独立地是氢，烯丙基，任选取代的C 1 -C 10烷基或C 3 -C 6环烷基，任选取代的C 7 -C 15苄基，任选取代的C 6 -C 15芳基，任选取代的C 6 -C 15杂原子的环，任选取代的C 3 -C 20 酰基，任选取代的C 3 -C 20酰胺或任选取代的C 3 -C 20硫代酰胺; 并且R 5是任选取代的C 1 -C 20烷基或C 3 -C 6环烷基，任选取代的C 7 -C 15苄基，任选取代的C 6 -C 15芳基，任选取代的C 6 -C 15杂原子的环，任选取代的C 1 -C 10烷氧基， C 1 -C 6烷基，C 1 -C 6卤代烷基，C 1 -C 6烷基，C 1 -C 6烷基，C 1 -C 6卤代烷基，C 1 -C 6卤代烷基， 烷氧基，C1-C6卤代烷氧基，C1-C6烷硫基，烷基砜和芳基砜，以及R3和R4同时为氢，R5为甲基，羟基，苯基或苯基胺的情况。